The ultimate goal of this project is to study the regulation of hormone response by extracellular environment and by the target cells themselves. A long term cell culture which retains its hormone sensitivity has been developed from fetal rat liver. Studies on cyclic AMP mediated hormones such as glucagon and Epinephrine have been emphasized initially, because of their relatively well established mode of action. One culture condition has been observed, which causes acute disappearance of hormone responses. This observation is being studied to determine whether the loss of hormone sensitivity is related to culture conditions and whether it is relevant to regulation of cell metabolism.